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Goro Takahashi, Takeshi Yamada, Takuma Iwai, Kohki Takeda, Michihiro Koizumi, Seiichi Shinji, Eiji Uchida
BACKGROUND: The self-expanding metallic stent (SEMS) provides effective decompression for patients with malignant large bowel obstruction (MLBO); however, mechanical damage to malignant cells from insertion may negatively affect prognosis, similar to surgical manipulation, and its oncological safety is unclear. We examined mechanical damage from SEMS placement using circulating cell-free DNA (cfDNA) and circulating tumor DNA (ctDNA). METHODS: Between 1 November 2014 and 30 June 2017, 35 MLBO patients were analyzed, comprising 25 SEMS patients and 10 transanal decompression tube (TDT) patients (control)...
December 12, 2017: Annals of Surgical Oncology
Adnana Paunel-Görgülü, Max Wacker, Mouhamed El Aita, Shoreshfan Hassan, Georg Schlachtenberger, Antje Deppe, Yeong-Hoon Choi, Elmar Kuhn, Thorsten O Mehler, Thorsten Wahlers
Cardiopulmonary bypass (CPB) provokes inflammation culminating in organ dysfunction and increased mortality. Recently, neutrophil extracellular traps (NETs) have been found to be involved in a variety of cardiovascular diseases promoting tissue and organ injury. Here, we aimed to elaborate the proinflammatory potential of circulating cell-free (cf)DNA in patients undergoing cardiac surgery with CPB. Plasma was collected pre- and postoperatively as well as at d1, d3, d5 and d8 after surgery. At d1, we found circulating cfDNA levels to be significantly increased in patients with prolonged CPB duration (>100 min) when compared to those with shorter CPB times (CPB < 100 min)...
December 12, 2017: Scientific Reports
I J Wilson, R K Burchell, A J Worth, S E Burton, K R Gedye, K J Clark, K R Crosse, M Jack, T F Odom, S J De Grey, K M S McGlade, S C Tomlin, N Lopez-Villalobos, A Gal
BACKGROUND: Cell-free DNA (cfDNA) comprises short, double-stranded circulating DNA sequences released from damaged cells. In people, cfDNA concentrations correlate well with disease severity and tissue damage. No reports are available regarding cfDNA kinetics in dogs. OBJECTIVES/HYPOTHESIS: Cell-free DNA will have a short biological half-life and would be able to stratify mild, moderate, and severe tissue injury. Our study aims were to determine the kinetics and biological half-life of cfDNA and to contrast them with those of creatine kinase (CK)...
December 12, 2017: Journal of Veterinary Internal Medicine
Linlin Yan, Yanhui Chen, Jiyuan Zhou, Hong Zhao, Henghui Zhang, Guiqiang Wang
OBJECTIVES: Circulating cell-free DNA (cfDNA) is a potential biomarker for tumor diagnosis. Hepatocyte damage is characteristic component of the pathobiology of hepatocellular carcinoma (HCC), which would be expected to result in substantial leakage of cfDNA into the circulation. However, the diagnostic value of cfDNA levels for HCC remains unclear. METHODS: Plasma samples were collected from 24 HCC patients and 62 HBV-related liver fibrosis patients. Plasma cfDNA levels was quantified by Qubit method...
December 8, 2017: International Journal of Infectious Diseases: IJID
Gabriel Beikircher, Walter Pulverer, Manuela Hofner, Christa Noehammer, Andreas Weinhaeusel
DNA methylation is a chemically stable key-player in epigenetics. In the vertebrate genome the 5-methyl cytosine (5mC) has been found almost exclusively in the CpG dinucleotide context. CpG dinucleotides are enriched in CpG islands very frequently located within or close to gene promoters. Analyses of DNA methylation changes in human diagnostics have been conducted classically using methylation-sensitive restriction enzymes (MSRE). Since the discovery of bisulfite conversion-based sequencing and PCR assays, MSRE-based PCR assays have been less frequently used, although especially in the field of cancer epigenetics MSRE-based genome-wide discovery and targeted screening applications have been and are still performed successfully...
2018: Methods in Molecular Biology
A K Krug, D Enderle, C Karlovich, T Priewasser, S Bentink, A Spiel, K Brinkmann, J Emenegger, D G Grimm, E Castellanos-Rizaldos, J W Goldman, L V Sequist, J-C Soria, D R Camidge, S M Gadgeel, H A Wakelee, M Raponi, M Noerholm, J Skog
Background: A major limitation of circulating tumor DNA (ctDNA) for somatic mutation detection has been the low level of ctDNA found in a subset of cancer patients. We investigated whether using a combined isolation of exosomal RNA (exoRNA) and cell-free DNA (cfDNA) could improve blood-based liquid biopsy for EGFR mutation detection in NSCLC patients. Patients and methods: Matched pretreatment tumor and plasma were collected from 84 patients enrolled in TIGER-X (NCT01526928), a Ph1/2 study of rociletinib in mutant EGFR NSCLC patients...
December 5, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Myung Han Hyun, Jae Sook Sung, Eun Joo Kang, Yoon Ji Choi, Kyong Hwa Park, Sang Won Shin, Sung Yong Lee, Yeul Hong Kim
We used computed tomography (CT) to explore the prognostic value of cell-free (cf) DNA quantification and its predictive efficacy over time after chemotherapy in non-small-cell lung cancer (NSCLC) patients. In total, 177 NSCLC patients were enrolled in a prospective biomarker trial. Consecutive paired blood collection was performed to determine cfDNA concentrations at baseline CT and throughout serial follow-ups. The best cfDNA cut-off value to predict progression-free and overall survival was determined using X-tile analysis...
November 7, 2017: Oncotarget
Alexander W Wyatt, Matti Annala, Rahul Aggarwal, Kevin Beja, Felix Feng, Jack Youngren, Adam Foye, Paul Lloyd, Matti Nykter, Tomasz M Beer, Joshi J Alumkal, George V Thomas, Robert E Reiter, Matthew B Rettig, Christopher P Evans, Allen C Gao, Kim N Chi, Eric J Small, Martin E Gleave
Background: Real-time knowledge of the somatic genome can influence management of patients with metastatic castration-resistant prostate cancer (mCRPC). While routine metastatic tissue biopsy is challenging in mCRPC, plasma circulating tumor DNA (ctDNA) has emerged as a minimally invasive tool to sample the tumor genome. However, no systematic comparisons of matched "liquid" and "solid" biopsies have been performed that would enable ctDNA profiling to replace the need for direct tissue sampling...
December 1, 2017: Journal of the National Cancer Institute
Anna-Lena Volckmar, Holger Sültmann, Anja Riediger, Thoas Fioretos, Peter Schirmacher, Volker Endris, Albrecht Stenzinger, Steffen Dietz
Recently, many genome-wide profiling studies provided insights into the molecular background of major cancer types. The deeper understanding of the genetic alterations and their functional consequences leveraged the discovery of novel therapeutic opportunities, improving clinical management of cancer patients. While tissue-based molecular patient stratification is the gold standard for precision medicine, it has certain limitations: Tissue biopsies are risky invasive sampling procedures and may not represent the entire tumor due to genetic heterogeneity...
December 5, 2017: Genes, Chromosomes & Cancer
H Hunt, N Cave, J Bridges, K Gedye, K Hill
BACKGROUND: Plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration is increased in dogs with myocardial dysfunction, and cell-free DNA (cfDNA) increases in numerous disease states. In humans, both of these biomarkers can be altered after endurance exercise. OBJECTIVE: To investigate the effect of prolonged strenuous exercise on circulating NT-proBNP and cfDNA concentrations in working farm dogs. ANIMALS: Six healthy, privately owned working farm dogs (4 Huntaways and 2 heading dogs) from the same hill country farm in New Zealand...
December 2, 2017: Journal of Veterinary Internal Medicine
John H Strickler, Jonathan M Loree, Leanne G Ahronian, Aparna R Parikh, Donna Niedzwiecki, Allan Andresson Lima Pereira, Matthew McKinney, W Michael Korn, Chloe E Atreya, Kimberly C Banks, Rebecca J Nagy, Funda Meric-Bernstam, Richard B Lanman, AmirAli Talasaz, Igor F Tsigelny, Ryan B Corcoran, Scott Kopetz
"Liquid biopsy" approaches analyzing cell-free DNA (cfDNA) from the blood of cancer patients are increasingly utilized in clinical practice. However, it is not yet known whether cfDNA sequencing from large cancer patient cohorts can detect genomic alterations at frequencies similar to those observed by direct tumor sequencing, and whether this approach can generate novel insights. Here, we report next-generation sequencing data from cfDNA of 1,397 colorectal cancer (CRC) patients. Overall, frequencies of genomic alterations detected in cfDNA were comparable to those observed in three independent tissue-based CRC sequencing compendia...
December 1, 2017: Cancer Discovery
Mathieu Chicard, Leo Colmet Daage, Nathalie Clement, Adrien Danzon, Mylene Bohec, Virginie Bernard, Sylvain Baulande, Angela Bellini, Paul Deveau, Gaelle Pierron, Eve Lapouble, Isabelle Janoueix-Lerosey, Michel Peuchmaur, Nadège Corradini, Anne-Sophie Desfachelles, Dominique Valteau-Couanet, Jean Michon, Valerie Combaret, Olivier Delattre, Gudrun Schleiermacher
BACKGROUND: Neuroblastoma (NB) displays important clinical and genetic heterogeneity, with emergence of new mutations at tumor progression. PATIENTS AND METHODS: To study clonal evolution during treatment and follow-up, an innovative method based on circulating cell-free DNA (cfDNA) analysis by whole exome sequencing (WES) paired with target sequencing was realized in sequential liquid biopsy samples of 19 NB patients. RESULTS: WES of the primary tumor and cfDNA at diagnosis showed overlap of Single Nucleotide Variants (SNVs) and Copy Number Alterations (CNAs), with 41% and 93% of all detected alterations common to the primary NB and cfDNA...
November 30, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Tongbo Wu, Wei Chen, Ziyu Yang, Haocheng Tan, Jiayu Wang, Xianjin Xiao, Mengyuan Li, Meiping Zhao
Sensitive detection of the single nucleotide variants in cell-free DNA (cfDNA) may provide great opportunity for minimally invasive diagnosis and prognosis of cancer and other related diseases. Here, we demonstrate a facile new strategy for quantitative measurement of cfDNA mutations at low abundance in the cancer patients' plasma samples. The method takes advantage of a novel property of lambda exonuclease which effectively digests a 5'-fluorophore modified dsDNA with a 2-nt overhang structure and sensitively responds to the presence of mismatched base pairs in the duplex...
November 28, 2017: Nucleic Acids Research
Tao Jiang, Xuefei Li, Jianfei Wang, Chunxia Su, Wenbo Han, Chao Zhao, Fengying Wu, Guanghui Gao, Wei Li, Xiaoxia Chen, Jiayu Li, Fei Zhou, Jing Zhao, Weijing Cai, Henghui Zhang, Bo Du, Jun Zhang, Shengxiang Ren, Caicun Zhou, Hui Yu, Fred R Hirsch
Rationale To investigate whether the mutational landscape of circulating cell-free DNA (cfDNA) could predict and dynamically monitor the response to first-line platinum-based chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC). Methods Eligible patients were included and blood samples were collected from a phase III trial. Both cfDNA fragments and fragmented genomic DNA were extracted for enrichment in a 1.15M size panel covering exon regions of 1,086 genes. Molecular mutational burden (MMB) was calculated to investigate the relationship between molecular features of cfDNA and response to chemotherapy...
2017: Theranostics
Pasquale Pisapia, Francesco Pepe, Riccardo Smeraglio, Maria Russo, Danilo Rocco, Roberta Sgariglia, Mariantonia Nacchio, Caterina De Luca, Elena Vigliar, Claudio Bellevicine, Giancarlo Troncone, Umberto Malapelle
Background: Non small cell lung cancer (NSCLC) is diagnosed in most cases on small tissue samples, such as cytological preparations and histological biopsies; these limited tissue specimens may be not always sufficient for testing epidermal growth factor receptor (EGFR) mutations and other relevant predictive biomarkers. Cell-free DNA (cfDNA) can be used as a surrogate for EGFR mutational testing, whenever tissue is unavailable. However, the detection of gene mutations on cfDNA is challenging; in fact, the extremely low concentration of circulating tumor DNA requires the implementation of highly sensitive and validated next generation techniques...
October 2017: Journal of Thoracic Disease
Niki Karachaliou, Aaron E Sosa, Miguel Angel Molina, Margarita Centelles Ruiz, Rafael Rosell
Liquid biopsies have been heralded as a game changer in cancer management. Blood tests offer a minimally invasive, safe and sensitive complementary (or even alternative) approach for tissue biopsies. With lung cancer being the second most commonly diagnosed cancer and the leading cause of cancer deaths worldwide, due to the limitations of tissue sampling, liquid biopsies must urgently materialize in the clinic. In this short review, we will present the current applications of cell-free DNA (cfDNA) in lung cancer management, emphasizing on our own experience and previous work...
October 2017: Journal of Thoracic Disease
Michely V Andreatta, Victor M Curty, João Victor S Coutinho, Miguel Ângelo A Santos, Paula F Vassallo, Nuno F de Sousa, Valério G Barauna
PURPOSE: The aims of this study were: a) to evaluate whether cell-free DNA (cfDNA) levels increase immediately after an acute light and heavy resistance exercise (RE) bout, and b) to whether cfDNA levels are associated with functional muscle capacity until 48hrs after exercise session. METHODS: Twenty healthy volunteers performed 3 sets of the leg press resistance exercise with 80% of 1RM (RE80) or 40% of 1RM (RE40) with similar exercise volume. Blood lactate was measured after completion of the 3 sets...
November 28, 2017: International Journal of Sports Physiology and Performance
Jesus Duque-Afonso, Miguel Waterhouse, Dietmar Pfeifer, Marie Follo, Justus Duyster, Hartmut Bertz, Jürgen Finke
Cell-free DNA (cfDNA) isolated from plasma or serum has received increasing interest for diagnostic applications in pregnancy, solid tumors and solid organ transplantation. The reported clinical usefulness of cfDNA obtained from plasma or serum in patients undergoing allogeneic cell transplantation (alloHSCT) is scarce. OBJECTIVE: To analyze the potential clinical utility of cfDNA chimerism analysis after alloHSCT. DESIGN AND METHODS: A total of 196 samples obtained from 110 patients were investigated for their chimeric status both in peripheral blood and plasma using standard PCR for microsatellite amplification...
November 24, 2017: Clinical Biochemistry
Jacqueline F Wang, Xingxiang Pu, Xiaoshan Zhang, Ken Chen, Yuanxin Xi, Jing Wang, Xizeng Mao, Jianhua Zhang, John V Heymach, Mara B Antonoff, Wayne L Hofstetter, Reza J Mehran, David C Rice, Jack A Roth, Boris Sepesi, Stephen G Swisher, Ara A Vaporciyan, Garrett L Walsh, Qing H Meng, Kenna R Shaw, Agda Karina Eterovic, Bingliang Fang
BACKGROUND: Next-generation sequencing of cell-free DNA (cfDNA) has been shown to be a useful noninvasive test for detecting mutations in solid tumors. METHODS: Targeted gene sequencing was performed with a panel of 263 cancer-related genes for cfDNA and genomic DNA of peripheral blood mononuclear cells (PBMCs) obtained from presurgical specimens of 6 lung cancer patients, and mutation calls in these samples were compared with those of primary tumors and corresponding patient-derived xenografts (PDXs)...
November 27, 2017: Cancer
S Valpione, G Gremel, P Mundra, P Middlehurst, E Galvani, M R Girotti, R J Lee, G Garner, N Dhomen, P C Lorigan, R Marais
INTRODUCTION: Tumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients. MATERIALS AND METHODS: A prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients...
November 23, 2017: European Journal of Cancer
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